Diabetes mellitus is a metabolic disease which currently afflicts some 16 million in the US and 100 million people worldwide. In the US, diabetes and its associated complications are the seventh leading cause of death. Effective management of diabetes requires regular measurement of blood sugar, and improvements in glucose sensing technology will enable superior care and regulation of diabetic blood sugar. The focus of this research project is to develop and characterize a minimally invasive nanoparticle-based optical sensor for transcutaneous glucose monitoring in interstitial fluid in subdermal skin tissue. The sensor implant responds to changes in interstitial glucose levels by changing its light scattering properties (turbidity) which are detected via non-invasive low-coherence interferometry. Significant long-term performance tests have been conducted demonstrating that the glucose-sensitive protein Concanavalin A, the glucose-recognition element of the sensor, retains necessary functionality at body temperature for over one year. These stability test data combined with enhanced specificity of the interferometry signal will ensure reliable and accurate performance of the affinity sensor over many months. We plan to thoroughly assess the role of nanoparticles in the glucose-dependent turbidity amplification of the sensor. The sensor will be particularly designed to generate a significant change in light scattering over the range of physiological blood sugar. The developed sensor will be tested in vitro and preliminary in vivo in a rat model. The anticipated results of this study will be a miniaturized, biocompatible prototype of a turbidity sensor implant whose light scattering properties change significantly based on the concentration of glucose in interstitial fluid.